Synthesis,modification And Controlled Release Properties Of Core-shell Silica Drug Carriers With Hierarchical Pores

Driven by the advancement of material chemistry and nanomedicine,the establishment of drug delivery platforms provides an effective way to improve the efficacy of tumor treatment and reduce side effects.The drug molecules are loaded in the nanocarriers with excellent biocompatibility and delivered to a specific lesion site,then the loaded-drug molecules are released under a certain stimulation,which would control the release of drug in space and dose,and reduce the damage to normal tissue cells.Silica nanoparticle has become a promising nanocarrier because of their unique properties and the ability to efficiently load drugs.In this paper,core-shell silica nanoparticles with hierarchical pores are synthesized for drug carriers,using biomolecules and polymers as gated keeper to establish a stimulus-responsive drug controlled release system.To further improve the controlled release properties of drug carriers,the blue/green carbon quantum dots as fluorescent markers are used to monitor the process of drug release in vitro.The main research contents and conclusions are as follows:(1)Synthesis of core-shell silica particles with hierarchical pores and p H responsive release propertyThe microemulsion method was used to synthesize core-shell silica particles with a large dendritic inner pores and a mesoporous shell.The tiopronin as a model drug was loaded in drug carriers,and the p H-responsive polyethyleneimine(PEI)was selected as a gate keeper and a capping agent to encapsulate the drug.The drug release behavior in simulated release solution under different p H was investigated.Experimental results showed that PEI modified silica nanocarrier exhibits excellent pH-responsive drug release behavior for tiopronin.(2)Synthesis of hierarchical porous silica modified with blue carbon quantum dot and redox/enzyme dual responsive drug release propertiesAccording to the presence of hyaluronidase and high concentration of reducing substances in tumor microenvironment,the redox/enzyme-responsive drug release system was designed and fabricated,using hyaluronic acid(HA)and oxidized glutathione(GSSG)as gate keeper and the anticancer drug doxorubicin(Dox)as model drug.Blue carbon quantum dots(CDs)were introduced as fluorescent markers to monitor drug release process according to the changes of fluorescence signal.The experimental results showed that the prepared dual-responsive drug release carrier exhibits excellent response to different concentrations of hyaluronidase and glutathione release solution.The change trend of fluorescent intensity in the release solution was consistent with that of drug release rate,showing the monitoring effect of fluorescent signal on the drug release process.(3)Synthesis of hierarchical porous silica modified with responsive blue carbon dots and p H/enzyme responsive drug release propertiesBased on the presence of hyaluronidase and weak acidity in tumor tissue,p H responsive chitosan(CS)was used as gated molecule and carbon quantum dots modified with hyaluronic acid(CDHA)was used as enzyme responsive gating molecules and capping agent to encapsulate Dox.The release test showed that the prepared CDHA endows the drug carrier with fluorescent properties and presents excellent responsiveness to HA.Meanwhile,CS displayed favourable responsiveness to the weak acidity in release medium.(4)Synthesis of hierarchical porous silica modified with green carbon dots and redox/p H responsive drug release propertiesIn this chapter,a dual responsive silica drug delivery system was constructed based on cystine(Cy)and PEI.Cy could respond to the reducing substances in tumor environment and PEI was used for p H stimulus-response layer to seal the drug carrier.Since the blue fluorescent dots were not completely suitable for living organisms,green carbon dots(g CDs)were prepared for fluorescent labeling and drug release monitoring so as to avoid the interference of blue fluorescence of organism.The text results showed that the dual responsive silica drug carriers present excellent responsive drug release behavior in vitro for GSH and p H.Simultaneously,g CDs imparted the carrier with fluorescent performance and played a monitoring role in the drug release process.